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首页> 外文期刊>Epigenetics & Chromatin >Histone H1 variant-specific lysine methylation by G9a/KMT1C and Glp1/KMT1D
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Histone H1 variant-specific lysine methylation by G9a/KMT1C and Glp1/KMT1D

机译：G9a / KMT1C和Glp1 / KMT1D对组蛋白H1变体特异的赖氨酸甲基化

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Background The linker histone H1 has a key role in establishing and maintaining higher order chromatin structure and in regulating gene expression. Mammals express up to 11 different H1 variants, with H1.2 and H1.4 being the predominant ones in most somatic cells. Like core histones, H1 has high levels of covalent modifications; however, the full set of modifications and their biological role are largely unknown. Results In this study, we used a candidate screen to identify enzymes that methylate H1 and to map their corresponding methylation sites. We found that the histone lysine methyltransferases G9a/KMT1C and Glp1/KMT1D methylate H1.2 in vitro and in vivo, and we mapped this novel site to lysine 187 (H1.2K187) in the C-terminus of H1. This H1.2K187 methylation is variant-specific. The main target for methylation by G9a in H1.2, H1.3, H1.5 and H1.0 is in the C-terminus, whereas H1.4 is preferentially methylated at K26 (H1.4K26me) in the N-terminus. We found that the readout of these marks is different; H1.4K26me can recruit HP1, but H1.2K187me cannot. Likewise, JMJD2D/KDM4 only reverses H1.4K26 methylation, clearly distinguishing these two methylation sites. Further, in contrast to C-terminal H1 phosphorylation, H1.2K187 methylation level is steady throughout the cell cycle. Conclusions We have characterised a novel methylation site in the C-terminus of H1 that is the target of G9a/Glp1 both in vitro and in vivo. To our knowledge, this is the first demonstration of variant-specific histone methylation by the same methyltransferases, but with differing downstream readers, thereby supporting the hypothesis of H1 variants having specific functions.
机译：背景接头组蛋白H1在建立和维持高级染色质结构以及调节基因表达中起关键作用。哺乳动物最多可表达11种不同的H1变异体，其中H1.2和H1.4是大多数体细胞中的主要变异体。像核心组蛋白一样，H1具有高水平的共价修饰。然而，修饰的全套及其生物学作用在很大程度上尚不清楚。结果在这项研究中，我们使用了候选筛选来鉴定使H1甲基化的酶并定位其相应的甲基化位点。我们发现在体外和体内，组蛋白赖氨酸甲基转移酶G9a / KMT1C和Glp1 / KMT1D甲基化H1.2，并且我们将此新位点映射到H1 C端的赖氨酸187（H1.2K187）。 H1.2K187甲基化是变体特异性的。 G9a在H1.2，H1.3，H1.5和H1.0中甲基化的主要目标是在C端，而H1.4在N端的K26（H1.4K26me）处优先被甲基化。我们发现这些标记的读数是不同的。 H1.4K26me可以招募HP1，但H1.2K187me不能招募。同样，JMJD2D / KDM4仅逆转H1.4K26甲基化，从而清楚地区分这两个甲基化位点。此外，与C端H1磷酸化相反，在整个细胞周期中H1.2K187甲基化水平稳定。结论我们已经在H1的C末端表征了一个新的甲基化位点，该位点在体内和体外都是G9a / Glp1的靶标。据我们所知，这是通过相同的甲基转移酶，但下游读者不同而对变体特异性组蛋白甲基化的首次证明，从而支持了具有特定功能的H1变体的假说。

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